Segmental Heterogeneity of Vasa Vasorum Neovascularization in Human Coronary Atherosclerosis

Abstract

Objectives To investigate the role of coronary vasa vasorum (VV) neovascularization in the progression and complications of human coronary atherosclerotic plaques. Background Accumulating evidence supports an important role of VV neovascularization in atherogenesis and lesion location determination in coronary artery disease. VV neovascularization can lead to intraplaque hemorrhage, which has been identified as a promoter of plaque progression and complications like plaque rupture. We hypothesized that distinctive patterns of VV neovascularization and associated plaque complications can be found in different stages of human coronary atherosclerosis. Methods Hearts from 15 patients (age 52±5, mean±SEM) were obtained at autopsy, perfused with Microfil™ and subsequently scanned with micro-computed tomography (micro-CT). Two-cm-segments (n=50) were histologically classified as either normal (n=12), nonstenotic plaque (<50% stenosis, n=18), or calcified (n=10) or non-calcified (n=10) stenotic plaque. Micro-CT images were analyzed for VV density (#/mm2), VV vascular area fraction (mm2/mm2) and VV endothelial surface fraction (mm2/mm3). Histological sections were stained for Mallory’s (iron), von Kossa (calcium) and glycophorin-A (erythrocyte fragments) as well as endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α). Results VV density was higher in segments with non-stenotic and non-calcified stenotic plaques as compared to normals (3.36±0.45, 3.72±1.03 vs. 1.16±0.21, P<0.01). In calcified stenotic plaques VV spatial density was lowest (0.95±0.21, P<0.05 vs. non-stenotic and non-calcified stenotic plaque). The amount of iron and glycophorin A was significantly higher in non-stenotic and stenotic plaques as compared to normals, and correlated with VV density (Kendall-Tau correlation-coefficient 0.65 and 0.58 respectively, P<0.01). Moreover, relatively high amounts of iron and glycophorin A were found in calcified plaques. Further immunohistochemical characterization of VV revealed positive staining for eNOS and TNF-α but not VEGF. Conclusion Our results support a possible role of VV neovascularization, VV rupture and intraplaque hemorrhage in the progression and complications of human coronary atherosclerosis.

Abdominal aortic aneurysm and histological, clinical, radiological correlation

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Vascular Normalization as a Therapeutic Strategy for Malignant and Nonmalignant Disease

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Impaired Thymic Export and Increased Apoptosis Account for Regulatory T Cell Defects in Patients with Non-ST Segment Elevation Acute Coronary Syndrome

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